Subsenescent telomere lengths in fibroblasts immortalized by limiting amounts of telomerase
Subsenescent telomere lengths in fibroblasts immortalized by limiting amounts of telomerase
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DOI：
10.1074/jbc.275.14.10072
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发表时间：
2000-04-07
影响因子：
4.8
通讯作者：
Wright, WE
中科院分区：
文献类型：
--
作者：
Ouellette, MM;Liao, M;Wright, WE
表达人端粒酶催化成分(HTERT)的人成纤维细胞已经被跟踪了250-400个群体倍增，不出所料，在稳定的转染体的长期培养中，端粒酶活性下降，然而，端粒平均长度比衰老亲本细胞短几千个碱基的克隆继续增殖。虽然最长的端粒缩短了，但最短的端粒的大小保持不变。具有亚衰老端粒长度的细胞在用显性阴性的hTERT突变体抑制端粒酶活性后，又增殖了20倍。这些结果表明，在限制端粒酶活性的条件下，顺式作用信号可能会招募端粒酶作用于最短的端粒，反对细胞衰老的死亡阶段1机制受端粒位置效应(即当端粒变短时，长端粒沉默的亚端粒基因的表达)调节的假说，并表明催化活性的端粒酶不需要在非常短的端粒末端提供蛋白质封顶作用。
Human fibroblasts expressing the catalytic component of human telomerase (hTERT) have been followed for 250-400 population doublings, As expected, telomerase activity declined in long term culture of stable transfectants, Supprisingly, however, clones with average telomere lengths several kilobases shorter than those of senescent parental cells continued to proliferate. Although the longest telomeres shortened, the size of the shortest telomeres was maintained. Cells with subsenescent telomere lengths proliferated for an additional 20 doublings after inhibiting telomerase activity with a dominant-negative hTERT mutant. These results indicate that, under conditions of limiting telomerase activity, cis-acting signals may recruit telomerase to act on the shortest telomeres, argue against the hypothesis that the mortality stage 1 mechanism of cellular senescence is regulated by telomere positional effects (in which subtelomeric loci silenced by long telomeres are expressed when telomeres become short), and suggest that catalytically active telomerase is not required to provide a protein-capping role at the end of very short telomeres.